Department of Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York.
Department of Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York.
J Am Soc Cytopathol. 2022 Nov-Dec;11(6):345-351. doi: 10.1016/j.jasc.2022.06.007. Epub 2022 Jul 14.
At present, GATA binding protein 3 (GATA-3) is the most frequently used diagnostic immunohistochemical (IHC) marker for breast carcinoma (BC). However, it is not specific and has very low sensitivity for triple-negative BC (TNBC). SRY-box transcription factor 10 (SOX-10) and trichorhinophalangeal syndrome type 1 (TRPS-1) have been suggested for inclusion in the diagnostic workup of TNBC. TRPS-1 has not been established in cytology specimens as a diagnostic IHC marker for metastatic BC (MBC). Hence, in the present study we evaluated the utility of TRPS-1 in diagnosing MBC in cytology specimens.
MBC cases diagnosed on cytology specimens from January to October 2020 were included in the present study. Only cases with hormonal status available and ≥20 tumor cells on cell blocks were included in the study. The cell blocks were assessed for TRPS-1, GATA-3, and SOX-10 IHC marker positivity (intensity and percentage of tumor cells). The results were correlated with the specimen type (fine needle aspiration [FNA] versus body fluid) and various BC prognostic subgroups.
We analyzed 61 cases, including 33 body fluid and 28 FNA (13 lymph node, 10 bone, 2 liver, 2 soft tissue, and 1 lung) specimens. TRPS-1 had 97.2% positivity in ER/PR+ (estrogen receptor/progesterone receptor-positive) MBC compared with GATA-3, which had 100% positivity in the same group. TRPS-1 showed high positivity in 35 of 37 cases (94.6%) and intermediate positivity in 1 (2.6%) and was negative/low positive in 1 case (2.7%). In contrast, GATA-3 showed high positivity for all 37 cases (100%). SOX-10 showed positivity in only 1 of 37 cases (2.7%), with intermediate positivity. In the HER2+ (human epidermal growth factor receptor 2-positive) group, TRPS-1 showed high positivity in 5 of 7 cases (71.4%), intermediate positivity in 1 case (14.3%), and negativity in 1 case (14.3%). However, GATA-3 showed high positivity in 6 of 7 cases (85.7%) and negative/low positivity in 1 case (14.3%). SOX-10 was negative in all 7 cases. In TNBC, TRPS-1 showed high positivity in 16 of 17 cases (94%) and intermediate positivity in 1 (5.9%), and GATA-3 showed high positivity in 9 (53%), intermediate positivity in 2 (11.8%), and low positive/negative in 6 of the 17 cases (35.3%). TRPS-1 expression was significantly higher than GATA-3 expression for the number of positive cases (P = 0.07), mean percentage of positive tumor cells (P = 0.005), and intensity of reactivity (P = 0.005). SOX-10 expression was present in only 5 of 17 cases (29%), with a mean percentage of positivity in the tumor cells of 26.5% and intensity of 0.8. No differences were found in the IHC results between the different specimen types (FNA versus fluid) in any group.
TRPS-1 is a highly sensitive new diagnostic IHC marker for breast carcinoma, with a similar positivity rate in ER/PR+ and HER2+ BC compared with GATA-3 and a higher positivity rate than GATA-3 and SOX-10 in TNBC in cytology specimens. In particular, when only a few clusters of tumor cells are present on the cell block, TRPS-1 can be highly useful, because its mean percentage of positive tumor cells and intensity are higher than those of other IHC markers.
目前，GATA 结合蛋白 3（GATA-3）是乳腺癌（BC）最常用的诊断免疫组织化学（IHC）标志物。然而，它的特异性不高，对三阴性乳腺癌（TNBC）的敏感性很低。SOX-10 和 trichorhinophalangeal 综合征 1 型（TRPS-1）已被建议纳入 TNBC 的诊断。TRPS-1 尚未在细胞学标本中确立为转移性乳腺癌（MBC）的诊断 IHC 标志物。因此，在本研究中，我们评估了 TRPS-1 在诊断细胞学标本中的 MBC 的应用价值。
纳入 2020 年 1 月至 10 月间细胞学标本诊断为 MBC 的病例。仅纳入有激素状态且细胞块上有≥20 个肿瘤细胞的病例。评估细胞块的 TRPS-1、GATA-3 和 SOX-10 IHC 标志物阳性（强度和肿瘤细胞百分比）。结果与标本类型（细针抽吸[FNA]与体液）和各种 BC 预后亚组相关联。
我们分析了 61 例病例，包括 33 例体液和 28 例 FNA（13 例淋巴结、10 例骨、2 例肝、2 例软组织和 1 例肺）标本。TRPS-1 在 ER/PR+（雌激素受体/孕激素受体阳性）MBC 中的阳性率为 97.2%，GATA-3 在同一组中的阳性率为 100%。TRPS-1 在 37 例中的 35 例（94.6%）中呈高度阳性，1 例（2.6%）呈中度阳性，1 例（2.7%）呈阴性/弱阳性。相比之下，GATA-3 在所有 37 例中均呈高度阳性。SOX-10 在 37 例中仅 1 例（2.7%）呈阳性，呈中度阳性。在 HER2+（人类表皮生长因子受体 2 阳性）组中，TRPS-1 在 7 例中的 5 例（71.4%）呈高度阳性，1 例（14.3%）呈中度阳性，1 例（14.3%）呈阴性/弱阳性。然而，GATA-3 在 7 例中的 6 例（85.7%）呈高度阳性，1 例（14.3%）呈阴性/弱阳性。SOX-10 在所有 7 例中均呈阴性。在 TNBC 中，TRPS-1 在 17 例中的 16 例（94%）呈高度阳性，1 例（5.9%）呈中度阳性，GATA-3 在 9 例（53%）中呈高度阳性，2 例（11.8%）呈中度阳性，6 例（35.3%）呈弱阳性/阴性。在阳性病例数量（P=0.07）、肿瘤细胞阳性百分比（P=0.005）和反应强度（P=0.005）方面，TRPS-1 的表达明显高于 GATA-3。SOX-10 在 17 例中仅 5 例（29%）表达，肿瘤细胞阳性百分比平均为 26.5%，反应强度为 0.8。在任何一组中，不同标本类型（FNA 与体液）之间的 IHC 结果均无差异。
TRPS-1 是一种高度敏感的新的乳腺癌诊断 IHC 标志物，在 ER/PR+和 HER2+BC 中的阳性率与 GATA-3 相似，在 TNBC 中的阳性率高于 GATA-3 和 SOX-10。特别是当细胞块上只有少数簇肿瘤细胞时，TRPS-1 非常有用，因为它的肿瘤细胞阳性百分比和强度均高于其他 IHC 标志物。
